NM_002575.3:c.225C>G

Variant names:

• chr18-63895320-C-G
• rs200884637
• NM_002575.3:c.225C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_002575.3(SERPINB2):​c.225C>G​(p.Asn75Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.45

Genes affected

SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity PAI2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06493679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.225C>G	p.Asn75Lys	missense_variant	Exon 4 of 9		NP_001137290.1
SERPINB2	XM_024451192.2	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 8	1	NM_002575.3	ENSP00000299502.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461800 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.0020
DANN	Benign	0.41
DEOGEN2	Benign	0.10	T;T;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.38	T;.;T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.065	T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.2	.;L;L;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.77	N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.39	T;T;T;T;T
Sift4G	Uncertain	0.039	D;T;T;T;T
Polyphen		0.0010	.;B;B;.;.
Vest4		0.15, 0.14
MutPred		0.46		Gain of ubiquitination at N75 (P = 0.006);Gain of ubiquitination at N75 (P = 0.006);Gain of ubiquitination at N75 (P = 0.006);Gain of ubiquitination at N75 (P = 0.006);Gain of ubiquitination at N75 (P = 0.006);
MVP		0.26
MPC		0.016
ClinPred		0.25	T
GERP RS		-9.7
Varity_R		0.053
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200884637; hg19: chr18-61562554;